Search for mutations affecting protein structure in children of atomic bomb survivors: preliminary report.

Abstract

A total of 289,868 locus tests, based on 28 different protein phenotypes and using one-dimensional electrophoresis to detect variant proteins, has yielded one probable mutation in the offspring of "proximally exposed" parents, who received an estimated average gonadal exposure of 31 to 39 rem in the atomic bombings of Hiroshima and Nagak. There were no mutations in 208,196 locus tests involving children of "distally exposed" parents, who had essentially no radiation exposure. Studies of the genetic effects of atomic bombs have been in progress in Hiroshima and Nagasaki since 1946 (1-5). The first generation of studies was essentially morphological in nature. More recently, profiting from technological developments, studies have been undertaken at the cytogenetic (6, 7) and biochemical (8) levels. We present here a progress report on the results of the biochemical approach at approximately the midpoint of the study. No statistically significant difference between the children of exposed and control parents can be demonstrated at this time (nor was it expected at this juncture in the study). In addition to the timeliness of a progress report, however, the present publication is dictated by three other considerations. (i) The current intense interest in the genetic effects of low-level ionizing radiation has prompted a complete re-evaluation of 30 years of genetic studies on the effects of the atomic bombs; the present data can be integrated into that treatment. (fi) The control aspects of the data of this study can be combined with similar data from other studies to yield a direct estimate of the rate at which spontaneous mutation results in electrophoretic variants of proteins; this should be useful in planning the feasibility and magnitude of any other genetic studies of this type. (Wi) A wealth of data on biochemical variants in Japanese has accumulated during the past 7 years; this description should clear the way for the presentation of this information.

Cancer incidence in children and young adults did not increase relative to parental exposure to atomic bombs

“…The latest mortality study (Izumi et al, 2003) suggested that such exposure did not lead to increased cancer mortality rates in childhood and young adulthood among the offspring born in Hiroshima and Nagasaki. This finding is consistent with earlier studies of the cohort, which found no dose-dependent increases in mortality (Kato et al, 1966;Neel et al, 1974;Yoshimoto et al, 1991;Little et al, 1994), childhood cancer (Yoshimoto et al, 1990), untoward pregnancy outcomes (Neel and Schull, 1956;Otake et al, 1990), cytogenetic abnormalities (Awa et al, 1987), or loss of enzyme activity (Neel et al, 1988). However, because cancers with high survival rates could not be adequately evaluated by mortality data, the effects of parental irradiation on cancer risks among the offspring need to be examined using the cancer incidence data.…”

Recovery of a low mutant frequency after ionizing radiation-induced mutagenesis during spermatogenesis

“…Further, analyses of mutations in microsatellite DNA obtained from children born to atomic bomb survivors has demonstrated similar mutant frequencies among these children and children born to nonexposed parents [40,41]. An analysis of proteins by starch gel electrophoresis also found similar levels of mutation in offspring of atomic bomb survivors and children born to control parents [42].…”

Electrophoretic variants of blood proteins in Japanese I. Phosphoglucomutase-2 (PGM2)

“…As the purpose differed between the two studies, the method of the family study also differed in the two populations. For the Adult population, family study was pursued until a variant identical to that of the propositus was encountered , while in the case of the Child population, the purpose was specifically to examine parents (Neel et aL, 1980). In either population, while some families were cooperative, others were not or family members did not reside in Hiroshima or Nagasaki.…”

“…After a pilot study of A-bomb survivors, an electrophoretic study of children of survivors was undertaken, and interim reports were published (Neel et al, 1980;Satoh et al, 1982aSatoh et al, , 1982b. By the end of September 1982, a total of 11,534 children of proximally exposed parents and 9,092 children of distally exposed parents were examined for variants in a maximum of 30 protein systems, the number of systems examined differing from child to child.…”

“…By the end of September 1982, a total of 11,534 children of proximally exposed parents and 9,092 children of distally exposed parents were examined for variants in a maximum of 30 protein systems, the number of systems examined differing from child to child. Using the same procedure as that of Harris et al (1974) and Neel et al (1980), the number of equivalent locus tests was calculated as 543,664 for the exposed group and 386,706 for the control group. Since three and two fresh mutants were encountered respectively in the exposed group and the control group, giving mutation rates of 0.55x 10 -5 and 0.52x 10 -5 per locus per generation, it is clear that so far no measurable genetic effect due to A-bomb exposure of the parents has been observed.…”